Further studies are needed, but at present these preliminary results offer a new direction for therapeutic intervention in recipients of renal allografts with BKN.
. Longitudinal study of urinary excretion of phosphate, calcium, and uric acid in mutant NHERF-1 null mice. Am J Physiol Renal Physiol 290: F838 -F843, 2006. First published October 25, 2005 doi:10.1152/ajprenal.00374.2005.-NHERF-1 binds numerous renal protein targets, including the proximal tubule transporters Na ϩ /H ϩ exchanger 3 (NHE3) and Na ϩ -phosphate cotransporter 2a (Npt2a). Young NHERF-1 Ϫ/Ϫ male mice display defective targeting of Npt2a to apical membranes in the renal proximal tubule and manifest hypophosphatemia and increased urinary excretion of phosphate. The present studies describe the changes in the urinary excretion of phosphate, calcium, uric acid, and sodium in male and female wild-type and NHERF-1 null mice over a time period from 12 to 54 wk of age. Young male and female NHERF-1 Ϫ/Ϫ mice demonstrated increased urinary excretion of phosphate and urine phosphate/creatinine ratios. There was an age-related decline in the phosphate/ creatinine ratio in mutant mice such that there were no differences between wild-type and NHERF-1 Ϫ/Ϫ by 24 to 30 wk of age despite the continued presence of hypophosphatemia. Male and female NHERF-1 null mice also demonstrate increased urine calcium/creatinine and uric acid/creatinine ratios compared with wild-type controls. These studies indicate defects in the renal tubule transport of phosphate, calcium, and uric acid in NHERF-1 Ϫ/Ϫ male and female mice that could account for the increased deposition of calcium in the papilla of null mice. bone density and mineralization; hypophosphatemia; electrolyte excretion INACTIVATION OF THE GENE encoding the sodium-phosphate cotransporter 2a (Npt2a, NaPi IIa) results in increased urinary excretion of phosphate and calcium and a striking bone phenotype characterized by decreased bone density and mineralization (2). Interestingly, by mechanisms not well understood, the changes in bone resolve as the animals age. It has not been established, however, whether the changes in mineral excretion persist. Like the Npt2a null mouse, targeted gene deletion of the sodium-hydrogen exchanger regulator factor-1 (NHERF-1) results in animals with increased urinary excretion of phosphate and calcium (14). The present experiments were undertaken to determine whether there were age-related changes in the urinary excretion of phosphate, calcium, uric acid, and sodium in NHERF-1 Ϫ/Ϫ male and female animals. The results indicate that young male and female NHERF-1 null mice have increased urinary excretion of phosphate but that there is an age-related partial correction in the defect in phosphate transport. Both male and female NHERF-1 null mice also have increased urinary excretion of calcium and uric acid but, in contrast to the defect in phosphate excretion, the abnormalities persist throughout the period of observation up to 1 yr of age. The transient as well as the persistent changes in urinary mineral and electrolyte excretion in these mice predict urine prone to the formation of calcium and/or uric acid stones. Analysis of the mutant m...
9 (22.4), respectively, at the time of conversion therapy. During the follow-up (range, 1.5-34.6, months), a total of 13 patients had their first acute rejection following the conversion therapy, an annual incidence of less than 10% and none of these episodes resulted in graft loss. The salutary effects of sirolimus therapy following discontinuation of tacrolimus in patients with moderate to severe graft dysfunction due to allograft nephropathy even in high-risk patients improves kidney function and prevents acute rejection.
Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare disease caused by autoantibodies against the glomerular basement membrane. Atypical anti-GBM nephritis is clinically less aggressive and characterized by the absence of circulating autoantibodies to the basement membrane. A previously healthy 53-year-old white woman presented with a rising creatinine over a short observation period. Renal biopsy, urinary sediment, and laboratory testing confirmed the diagnosis of atypical anti-GBM disease. She received plasmapheresis, steroids, and cyclophosphamide. She developed hemorrhagic cystitis early in the treatment from oral cyclophosphamide and mycophenolate mofetil was substituted as a first-line drug. She responded favorably and continued on mycophenolate mofetil without evidence of relapse. Despite the absence of circulating autoantibodies, a diagnosis of atypical anti-GBM nephritis should not be excluded if a high index of clinical suspicion exists. Early renal biopsy should be considered. Mycophenolate mofetil may be a reasonable replacement for oral cyclophosphamide in the treatment of atypical anti-GBM disease when cyclophosphamide is contraindicated.
Blood pressure naturally rises with increasing age. The rate of change in blood pressure with age is regulated in part by genetic factors, but can also be altered through sustained dietary modification. Dietary approaches to modify blood pressure remain an important part of cardiovascular health promotion, which is especially important given the aging of the general population coupled with the increasing prevalence of obesity and metabolic disturbances. Specific modification of dietary components such as macronutrients and micronutrients could be helpful to lower blood pressure and alter the slope of blood pressure change whereas nutritional supplements are less likely to have a substantial beneficial effect. Population-wide generalizations regarding diet are impractical as individualized strategies are more likely to be successful in facilitating long-term benefits in improving blood-pressure control. Consequently, more effort needs to be focused on evaluating data from large-scale observational and interventional studies and interpreting their information in a clinically relevant manner, which is likely to be helpful for individual patients. Providing education on the relationship between diet and blood pressure from an early age is most likely to produce tangible benefits.
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